Pharmacogenomic Association of Nonsynonymous SNPs in SIGLEC12, A1BG, and the Selectin Region and Cardiovascular Outcomes
(2013) In Hypertension 62(1). p.48-54- Abstract
- We sought to identify novel pharmacogenetic markers associated with cardiovascular outcomes in patients with hypertension on antihypertensive therapy. We genotyped a 1:4 case:control cohort (n=1345) on the Illumina HumanCVD Beadchip from the INternational VErapamil SR-Trandolapril STudy (INVEST), where participants were randomized to a -blocker strategy or a calcium channel blocker strategy. Genome-spanning single nucleotide polymorphism (SNP)xtreatment interaction analyses of nonsynonymous SNPs were conducted in white and Hispanic race/ethnic groups. Top hits from whites were tested in Hispanics for consistency. A genetic risk score was constructed from the top 3 signals and tested in the Nordic Diltiazem study. SIGLEC12 rs16982743 and... (More)
- We sought to identify novel pharmacogenetic markers associated with cardiovascular outcomes in patients with hypertension on antihypertensive therapy. We genotyped a 1:4 case:control cohort (n=1345) on the Illumina HumanCVD Beadchip from the INternational VErapamil SR-Trandolapril STudy (INVEST), where participants were randomized to a -blocker strategy or a calcium channel blocker strategy. Genome-spanning single nucleotide polymorphism (SNP)xtreatment interaction analyses of nonsynonymous SNPs were conducted in white and Hispanic race/ethnic groups. Top hits from whites were tested in Hispanics for consistency. A genetic risk score was constructed from the top 3 signals and tested in the Nordic Diltiazem study. SIGLEC12 rs16982743 and A1BG rs893184 had a significant interaction with treatment strategy for adverse cardiovascular outcomes (INVEST whites and Hispanics combined interaction P=0.0038 and 0.0036, respectively). A genetic risk score, including rs16982743, rs893184, and rs4525 in F5, was significantly associated with treatment-related adverse cardiovascular outcomes in whites and Hispanics from the INVEST study and in the Nordic Diltiazem study (meta-analysis interaction P=2.39x10(-5)). In patients with a genetic risk score of 0 or 1, calcium channel blocker treatment was associated with lower risk (odds ratio [95% confidence interval]=0.60 [0.42-0.86]), and in those with a genetic risk score of 2 to 3, calcium channel blocker treatment was associated with higher risk (odds ratio [95% confidence interval]=1.31 [1.08-1.59]). These results suggest that cardiovascular outcomes may differ based on SIGLEC12, A1BG, F5 genotypes, and antihypertensive treatment strategy. These specific genetic associations and our risk score provide insight into a potential approach to personalized antihypertensive treatment selection. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3979647
- author
- McDonough, Caitrin W. ; Gong, Yan ; Padmanabhan, Sandosh ; Burkley, Ben ; Langaee, Taimour Y. ; Melander, Olle LU ; Pepine, Carl J. ; Dominiczak, Anna F. ; Cooper-DeHoff, Rhonda M. and Johnson, Julie A.
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- antihypertensive agents, -blockers, calcium channel blockers, genetic, variation, hypertension, pharmacogenetics
- in
- Hypertension
- volume
- 62
- issue
- 1
- pages
- 48 - 54
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000320302600013
- scopus:84880750541
- ISSN
- 1524-4563
- DOI
- 10.1161/HYPERTENSIONAHA.111.00823
- language
- English
- LU publication?
- yes
- id
- 1322eb9d-be3b-4bda-bf1b-d538eb9ebf94 (old id 3979647)
- date added to LUP
- 2016-04-01 11:14:31
- date last changed
- 2024-01-07 11:06:35
@article{1322eb9d-be3b-4bda-bf1b-d538eb9ebf94, abstract = {{We sought to identify novel pharmacogenetic markers associated with cardiovascular outcomes in patients with hypertension on antihypertensive therapy. We genotyped a 1:4 case:control cohort (n=1345) on the Illumina HumanCVD Beadchip from the INternational VErapamil SR-Trandolapril STudy (INVEST), where participants were randomized to a -blocker strategy or a calcium channel blocker strategy. Genome-spanning single nucleotide polymorphism (SNP)xtreatment interaction analyses of nonsynonymous SNPs were conducted in white and Hispanic race/ethnic groups. Top hits from whites were tested in Hispanics for consistency. A genetic risk score was constructed from the top 3 signals and tested in the Nordic Diltiazem study. SIGLEC12 rs16982743 and A1BG rs893184 had a significant interaction with treatment strategy for adverse cardiovascular outcomes (INVEST whites and Hispanics combined interaction P=0.0038 and 0.0036, respectively). A genetic risk score, including rs16982743, rs893184, and rs4525 in F5, was significantly associated with treatment-related adverse cardiovascular outcomes in whites and Hispanics from the INVEST study and in the Nordic Diltiazem study (meta-analysis interaction P=2.39x10(-5)). In patients with a genetic risk score of 0 or 1, calcium channel blocker treatment was associated with lower risk (odds ratio [95% confidence interval]=0.60 [0.42-0.86]), and in those with a genetic risk score of 2 to 3, calcium channel blocker treatment was associated with higher risk (odds ratio [95% confidence interval]=1.31 [1.08-1.59]). These results suggest that cardiovascular outcomes may differ based on SIGLEC12, A1BG, F5 genotypes, and antihypertensive treatment strategy. These specific genetic associations and our risk score provide insight into a potential approach to personalized antihypertensive treatment selection.}}, author = {{McDonough, Caitrin W. and Gong, Yan and Padmanabhan, Sandosh and Burkley, Ben and Langaee, Taimour Y. and Melander, Olle and Pepine, Carl J. and Dominiczak, Anna F. and Cooper-DeHoff, Rhonda M. and Johnson, Julie A.}}, issn = {{1524-4563}}, keywords = {{antihypertensive agents; -blockers; calcium channel blockers; genetic; variation; hypertension; pharmacogenetics}}, language = {{eng}}, number = {{1}}, pages = {{48--54}}, publisher = {{Lippincott Williams & Wilkins}}, series = {{Hypertension}}, title = {{Pharmacogenomic Association of Nonsynonymous SNPs in SIGLEC12, A1BG, and the Selectin Region and Cardiovascular Outcomes}}, url = {{http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.00823}}, doi = {{10.1161/HYPERTENSIONAHA.111.00823}}, volume = {{62}}, year = {{2013}}, }